Dolph Houben

117 Transplant chimerism in bone VCA 6 Introduction Segmental bone loss, often the result of limb-sparing resection of primary bone tumors, trauma, infection or failed primary reconstruction methods presents a challenging reconstructive problem. Current reconstructive options are problematic due to the risk of infection, non-union, stress fractures and implant failure. Living bone allotransplantation, a form of vascularized composite allotransplantation (VCA), is an alternative method with the potential to replace the missing bone with living bone closely matched in size and shape. Maintenance of VCA viability currently requires life-long drug immunosuppression. The significant expense of medication and monitoring, as well as risks of acute and chronic rejection, opportunistic infection, neoplasm, and organ toxicity, make this approach untenable for bone-only defects [1-3] [4, 5] . A method permitting drug-free bone allotransplant viability would quite possibly change clinical practice and improve patient outcomes. In experimental small animal studies, we have previously shown that angiogenesis from arteriovenous bundles or fascial flaps within the medullary canal of bone VCAs will generate a neoangiogenic autogenous circulation. The allogeneic vascular pedicle reconstructed simultaneously, is required only during the initial postoperative period, maintained with 2 weeks of drug therapy. Despite subsequent pedicle thrombosis, the implanted autogenous vessels maintain bone blood flow and improve bone healing and remodeling. Transplant chimerism has been demonstrated in areas of post-transplant new bone formation in a rat femur model [6] . These levels increase with time, eventually resulting in a near-complete substitution of the allotransplant from allogeneic to autogenic [7] . In this study, we have applied the same methods to test whether microchimerism also occurs in bone-only VCAs used to reconstruct a major bone defect in a large animal model with long-term survival. Transplant chimerism and autogenous bone remodeling may lead to future clinical applications of vascularized bone allotransplantation. Based on previous research, we hypothesized that bone-only VCAs will exhibit transplant chimerism, particularly in areas of new bone formation, facilitated by the development of an autogenous neoangiogenic circulation.